DESCRIPTION: The focus of these studies is to define the role of dendritic cells in salivary-associated mucosal immune responses in order to achieve the long-term objective of developing novel, clinically relevant immunization strategies to protect the oral cavity. The central hypothesis is that dendritic cells are of pivitol importance in the initiation and regulation of salivary IgA antibody responses. The individual hypotheses to be tested are: 1) antigen uptake and delivery to salivary-related lymphoid inductive sites is mediated by dendritic cells and potentiated by factors that activate the dendritic cell maturation program; 2) dendritic cell targeted immunomodulators determine the strength and outcome of salivary mucosal immune responses; and 3) dendritic cells play a role in the effector stage of salivary mucosal immune responses. These hypotheses will be tested by pursuing the following Specific Aims: AIM 1. To define conditions that enhance antigen localization in salivary-related mucosal inductive sites. This aim will phenotypically identify cell types involved in antigen uptake and translocation following intranasal immunization as well as investigate dendritic cell-targeted strategies to enhance antigen uptake and translocation to lymphoid inductive sites. AIM 2. To determine the role of dendritic cells in the inductive phase of salivary mucosal immune responses. This aim will employ an in vitro system to assess dendritic cell maturation and polarization by DC1 and DC2 inducing immunomodulators and utilize in vivo mucosal immunization protocols to activate and polarize dendritic cell populations for enhanced salivary IgA and systemic IgG antibody responses. AIM 3. To investigate the role of dendritic cells in the effector stage of salivary immune responses. This aim will utilize dendritic cell targeted immunization protocols to investigate the presence of salivary gland dendritic cell populations during mucosal effector responses, delineate mechanisms facilitating dendritic cell recruitment to salivary glands and investigate salivary gland dendritic cell chemotactic and accessory function during salivary IgA antibody responses. It is expected that a detailed understanding of the role of dendritic cells in the inductive and effector phases of salivary-associated mucosal immune responses will provide information essential to the development of new, clinically relevant vaccination strategies that will optimize protection of the oral cavity.